J. Regino Perez-Polo, Ph.D. 
Professor and Chair, Dept. of Biochemistry and Molecular Biology
Our long-term goals are to understand the mechan5isms of neuronal cell death and deficits associated with both acute and chronic trauma to the central nervous system at a molecular and cellular level. We have developed an array of interventions ranging from modified 
liposomal gene transfer, endogenous receptor antagonists and gene specific “decoy” inhibition of transcription factor binding to promoter sites as intervention approaches to therapy at the transcriptional level. Our hypothesis is that oxidative stress in the nervous system, caused by chronic or acute trauma, triggers inflammatory responses that result in the uncoupling of gene networks responsible for cell viability and function that result in the altered phenotypes associated with neural deficits present in injury, aging and Alzheimer’s Disease. In addition, we hypothesize that trauma-induced phosphorylation events affect organelle occupancy by proteins regulating cell death. For example, inflammatory cascades activated by trauma have genotoxic and energetic consequences that activate stress response genes via the NF-B transcription factor. Transcription factors bind to cognate DNA sequences that regulate stress response gene expression essential to survival and function. We believe that transcription factor binding to cognate
Figure. Demonstration of intranuclear and perinuclear BAX in CNS neurons.
DNA sequences is finely tuned by the specificity of the sequence, position within a promoter and protein-protein interactions with other sites on a promoter. Our ongoing studies focus on: the ß-amyloid generating BACE enzyme, the Bcl-protein family of genes, COX-2, iNOS, and the IL-1 cytokine. We rely on in vitro and working animal models for perinatal ischemia, spinal cord injury, and β-amyloid toxicity in rats, mice and guinea pigs. In vitro models used are the PC12 line and primary cultures derived from fetal and neonatal brain. We also rely on murine transgenic models of Alzheimer’s Disease and focal stroke in the aged rat. We use in vivo MRI techniques to assess damage and vascular changes in brain and spinal cordin addition to confocal immunocytochemistry to assess organelle function in response to oxidative stress. In vitro reporter constructs and transgenic models suitable to unraveling the role of the NF-kB transcription factor in transcriptional regulation of select genes are also used. In addition, we are applying genomic, proteomic and bioinformatics approaches to analyses of time course studies of post-traumatic injury response. Our animal studies look at outcomes to trauma and therapeutic molecular interventions in terms of locomotor functional recovery, cognitive and sensory outcomes, including central neuropathic pain. We also carry out gene transfer treatments for thermal trauma. Studies are supported in part by the NINDS, NICHD, NSF Israel/US Bilateral Agreement, Shriners and Clayton Foundations, and the Mission Connect Consortium and Sealy Program. Collaborative efforts include the Oregon Health Science Center, Baylor College of Medicine, University of Texas Houston Medical School, University of Leipzig, Germany, University of Montpellier, France, and Ben-Gurion University, Israel.
Selected Publications
Nesic O., N. Svrakic, G-Y. Xu, D. McAdoo, K.N. Westlund, C. E. Hulsebosch, Zeiming Ye , A. Galante, P. Soteropoulos, P. Tolias, W. Young, R.P. Hart and R. J. Perez-Polo. DNA microarray analysis of the contused spinal cord: The effect of NMDA receptor inhibition. JNR 68:406-423, 2002.
Cole, K.K. and J.R. Perez-Polo. Poly (ADP-Ribose) Polymerase Inhibition Prevents both Apoptotic-like Delayed Neuronal Death and Necrosis after H 2O 2 Injury. J. Neurochemistry, 82:19-29, 2002.
Qiu, J., X. Hu, O. Nesic, M.R. Grafe, D.K. Rassin, J. R. Perez-Polo. Effects of NF- k B Oligonucleotide “Decoys” on gene expression in p7 rat hippocampus after hypoxia/ischemia. J. Neurosci. Res. 77(1): 108-18, 2004.
Rossner, S., C. Lange-Dohna, U. Zeitschel and R. Perez-Polo. The Alzheimer’s disease b -secretase BACE1 is not a neuron-specific enzyme. J. Neurochemistry, 92:226-234, 2005
Hu, Xiaoming, Nesic-Taylor, Olivera, Qiu, Jingxin, Rea, Harriett C., Fabian, Roderick, Rassin David K., Perez-Polo, J. Regino. Activation of nuclear factor- kB signaling pathway by interleukin-1 after hypoxia/ischemia in neonatal rat hippocampus and cortex. J. Neurochemistry 93:26-37, 2005.
Nesic-Taylor O., Cittelly D, Ye Z, Xu GY, Unabia G, Lee JC, Svrakic NM, Liu XH, Youle RJ, Wood TG, McAdoo D, Westlund KN, Hulsebosch CE, Perez-Polo JR. Exogenous Bcl-xL fusion protein spares neurons after spinal cord injury. J. Neurosc. Res. 79(5):628-37, 2005.
Martin S.S., J. Regino Perez-Polo, K.M. Noppens, M. Grafe, Biphasic Changes in the Levels of poly(ADP-ribose) polymerase-1 and caspase 3in the immature brain following Hypoxia-Ischemia. IJDN 23(8):673-86, 2005.
Nesic, O., J. Lee, K.M. Johnson, Z. Ye, G-Y Xu, G.C. Unabia, T.G. Wood, D.J. McAdoo, K.N. Westlund, C.E. Hulsebosch, & J.R. Perez-Polo. Transcriptional profiling of spinal cord injury-induced central neuropathic pain. J. Neurochem., 95(4):998-1014, 2005.
Hu, Xiaoming, H.C. Rea, John E. Wiktorowicz & J.R. Perez-Polo. Proteomic Analysis of Hypoxia/Ischemia-Induced Alteration of Cortical Development and Dopamine Neurotransmission in Neonatal Rat. J. Proteome Res., 2,006.
Heinitz, K., Beck M., Schliebs R., JR Pere-Polo. Cholinotoxicity mediated by soluble oligomers of b -amyloid(1-42) differs from cholinotoxic effectgs of oxidative stress as revealed by gene expression analysis. Submitted to J. Neurochemistry. JNC 98:1930-1945, 2006.